One of the characteristics of an acute inflammatory response is the relatively rapid change in the plasma concentrations of certain proteins that have been collectively referred to as acute phase reactant proteins (APP). Whereas the kinetics and extent of the changes in plasma concentration of APP have been well documented, careful examination of changes in the synthetic and catabolic rates has not been made. In addition, the role that these proteins play in modulating the inflammatory response has not been defined. We plan to study the metabolism (synthesis and catabolism) of four APP (C3, C5, CRP, and ceruloplasmin) in normal rabbits and in rabbits with turpentine pleurisy, as a model of the inflammatory state. The proteins will be purified to homogeneity from rabbit serum using methods we have previously developed, and then labeled with 125I for the studies of catabolism. Synthesis will be measured by infusing 14C-amino acids intravenously and then determining the amount of 14C incorporated into specific protein. In order to characterize the mechanisms responsible for observed changes in synthetic rates, we will use in vitro experiments. Our initial hypothesis is that a soluble substance released during inflammation acts as a signal for the cells that are synthesizing the APP in question. Thus, we will screen plasmas from animals with inflammation to determine if any has an effect on the rate of APP synthesis by liver cells in vitro. If initial studies confirm this hypothesis, we will isolate and characterize the responsible signal using chromatographic, electrophoretic, and immunochemical methods. Finally, we will determine the role of these proteins in the modulation of inflammation. First, whole plasma from inflamed animals, and later purified proteins, will be infused into rabbits before turpentine is injected into the pleural space. The effect of the infusion on the course of the turpentine pleurisy will be monitored by measuring the volume of the pleural fluid and the cellular and protein content of the fluid, as well as systemic criteria of inflammation such as changes in blood leukocyte counts, fever, and changes in other APP plasma levels.